title: Trial Watch: Toll-like receptor agonists for cancer therapy.
abstract: Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of pattern recognition receptors has been attributed a critical role in the elicitation of anticancer immune responses, raising interest in the development of immunochemotherapeutic regimens based on natural or synthetic TLR agonists. In spite of such an intense wave of preclinical and clinical investigation, only three TLR agonists are currently licensed by FDA for use in cancer patients: bacillus Calmette-Guérin (BCG), an attenuated strain ofMycobacterium bovisthat operates as a mixed TLR2/TLR4 agonist; monophosphoryl lipid A (MPL), a derivative ofSalmonella minnesotathat functions as a potent agonist of TLR4; and imiquimod, a synthetic imidazoquinoline that activates TLR7. One year ago, in the August and September issues ofOncoImmunology, we described the main biological features of TLRs and discussed the progress of clinical studies evaluating the safety and therapeutic potential of TLR agonists in cancer patients. Here, we summarize the latest developments in this exciting area of research, focusing on preclinical studies that have been published during the last 13 mo and clinical trials launched in the same period to investigate the antineoplastic activity of TLR agonists.
authors.affiliation: Institut Gustave Roussy; Villejuif, France ; Université Paris-Sud/Paris XI; Le Kremlin-Bicêtre; Paris, France ; INSERM, U848; Villejuif, France.
authors.forename: Erika
authors.initials: E
authors.lastname: Vacchelli
authors.forename: Alexander
authors.initials: A
authors.lastname: Eggermont
authors.forename: Catherine
authors.initials: C
authors.lastname: Sautès-Fridman
authors.forename: Jérôme
authors.initials: J
authors.lastname: Galon
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
keywords: CpG oligodeoxynucleotides; Hiltonol™; damage-associated molecular patterns; lipopolysaccharide; picibanil; resiquimod